CREPT is a novel predictor of the response to adjuvant therapy or concurrent chemoradiotherapy in esophageal squamous cell carcinoma

Int J Clin Exp Pathol. 2019 Sep 1;12(9):3301-3310. eCollection 2019.

Abstract

CREPT has been shown to be highly expressed in most tumors and is associated with a poor prognosis, but the histologic characteristics of CREPT expression and its impact on clinical outcomes in esophageal squamous cell carcinoma (ESCC) are unclear. Therefore, we retroactively evaluated tissue microarrays (TMA) from 300 surgical cases, including 300 ESCC tissues and 161 adjacent non-tumor tissues, and pretreatment tumor biopsies from 113 concurrent chemoradiotherapy (CCRT) cases by immunohistochemistry (IHC). Notably, CREPT was increasingly expressed from non-cancerous tissues to atypical hyperplasia to tumor tissues (P < 0.01). Furthermore, patients were divided into low CREPT (≤ 8 scores) and high CREPT (> 8 scores) groups. Patients with high CREPT expressions had a worse overall survival (OS) (5-year OS: 40.9% vs. 50.1%, P=0.040) and disease-free survival (DFS) (5-year DFS: 29.5 vs. 43.0%; P=0.020) than those with low expressions. Nevertheless, only in the high CREPT subgroup did adjuvant therapy (AT) prolong the OS (5-year OS: 53.8 vs. 28.9%; P=0.020), especially for adjuvant radiotherapy (ART) (5-year OS: 85.7 vs. 28.9%; P=0.037; 5-year DFS: 85.7 vs. 22.3%; P=0.020). Surprisingly, high CREPT expressions endowed CCRT-treated patients with higher complete response rates (50% vs. 26%; P=0.018) and a favorable OS (3-year OS: 54.3 vs. 28.1%; P=0.046) compared to low expression. Overall, our findings indicate that CREPT is highly expressed in ESCC tissue compared with non-cancerous tissue and this feature is associated with a poor prognosis. Otherwise, patients with high CREPT expression were more sensitive to AT and CCRT. Moreover, CREPT could be a predictive immunohistochemical biomarker used to guide individualized clinical treatment.

Keywords: CREPT; Esophageal squamous cell carcinoma; adjuvant therapy; clinical individualized treatment; concurrent chemoradiotherapy.